摘要
目的 从胞内钙离子水平探讨氯氮平及其代谢产物对离体大鼠胰岛细胞内分泌功能的影响。方法 分别用低浓度（3．3mmol／L）和高浓度（16．7mmol／L）的葡萄糖Hank’s液经灌流装置孵育诱导，以终浓度为1μmol／L的氯氮平、去甲基氯氮平和N-氧化氯氮平分别作用于分离培养的大鼠胰岛细胞，并设两种浓度葡萄糖的空白对照组，以Fluo-4／AM为荧光探针，应用激光扫描共聚焦显微镜，动态监测不同药物作用于胰岛细胞后胞内钙荧光强度的变化。结果（1）低糖条件下，氯氮平组[（22±4）％]和去甲基氯氮平组[（49±6）％]胞内[Ca^2＋]；均低于空白对照组[（93±6）％；P〈0．01]；与未加处理因素前（0min）相比，氯氮平组和去甲基氯氮平组的胞内[Ca^2＋]随时间的延长而降低（P〈0．05—0．01），且氯氮平的抑制作用强于去甲基氯氮平（P〈0．01）。（2）高糖条件下，氯氮平组[（62±10）％]和去甲基氯氮平组[（18±8）％]胞内[Ca^2＋]；亦均低于空白对照组[（94±5）％；P〈0．01]；与未加处理因素前（0min）相比，氯氮平组和去甲基氯氮平组的胞内[Ca^2＋]；随时间的延长而降低（P〈0．05—0．01），其中去甲基氯氮平的抑制作用强于氯氮平（P〈0．01）。N-氧化氯氮平组对胞内[Ca^2＋]；的影响不大（P〉0．05）。结论 氯氮平及去甲基氯氮平均降低胰岛细胞胞内[Ca^2＋]；，从而抑制胰岛素分泌。
Objective To study the effects of clozapine and its metabolites on the intracellular Ca^2＋ concentration （ [ Ca^2＋ ] ） in cells of isolated rat islets. Methods Under low （3.3 mmol/L） or high glucose （16. 7 mmol/L）, the cells of isolated rat islets was treated with 1 μmol/L clozapine, desmethyl-clozapine and clozapine N-oxide respectively, blank control group was also set, [ Ca^2 ＋ ] i represented by fluorescence intensity was measured with laser scanning confocal microscope after cells were loaded with calcium sensitive fluorecent indicator Fluo-4/AM. Results Under low glucose, as compared with the blank control group,inhibitive effect on [ Ca^2＋ ]i in cells was found in clozapine group and desmethyl-clozapine group respectively （P 〈 0. 01 ）. As compared with the base line （0 min）, [ Ca^2＋ ] in cells was decreased with the prolonging time in clozapine group and desmethyl-clozapine group （P 〈 0. 05-0. 01 ）, and the inhibitive effect of clozapine was more intensive than desmethyl-clozapine （P 〈 0. 01 ）. Under high glucose, inhibitive effect on [ Ca^2＋ ]i in β-cells was also found in clozapine group and desmethyl-clozapine group respectively （P 〈 0.01 ） in comparison with the blank control. As compared with the base line （0 min）, [ Ca^2＋ ] in cells was also decreased with the prolonging time in clozapine group and desmethyl-clozapine group （ P 〈 0. 05-0. 01 ）,but the inhibitive effect of desmethyl-clozapine was more intensive than clozapine （P 〈 0. 01 ）. However,, no effect was found in clozapine N-oxide group under low or high glucose （ P 〉 0. 05 ）. Conclusion Both clozapine and desmethyl-clozapine can inhibit insulin secretion by inhibiting [ Ca^2 ＋ ] in cells of isolated rat islets.
出处
《中华精神科杂志》
CAS
CSCD
北大核心
2006年第4期220-223,共4页
Chinese Journal of Psychiatry
关键词
氯氮平
生物转化
胰岛
钙
Clozapine
Biotransformation
Islets of Langerhans
Calcium
